Staph

Question 0

Staph aureus epidemiology

Answer 0

Frequent colonizer of skin, mucous, nares (30-40%)
 - hospitalized, immunocompromised (most common HAI)
 - diabetics
 - drug users
 - catheters, devices
 - community = sports, jails (PVL toxin)
Identify strains via
 - serology
 - susceptibility to bacteriophages
 - ribotype (RNA sequence)
 - DNA sequence - protein A, coagulase
 - DNA fingerprinting (gel electrophoresis)

Question 1

Overview of staphylococcus

Answer 1

Major cause of hospital bacteremia (aureus, epidermidis)

• catheters, devices colonized from skin
• up to 60% resistant to methicillin -> vanco (some resistant)
• high morbidity, mortality

Gram + cocci in clusters
Facultative anaerobes
- Catalase + (H202 -> H2 + H2O) - vs Streptococcus
Coagulase - activates fibrinogen in plasma
- aureus positive, others negative

Aureus - 
Epidermidis
Saprophyticus
Hemolyticus
Hominis

Question 2

Staph aureus toxin-mediated disease

Answer 2

Toxin alone can reproduce disease in animals
Antibiotics may not be useful once disease presents!

Toxin-only
- contamination -> enterotoxin -> diarrhea
Colonization -> toxin (requires some growth in humans)
- toxic shock
- scalded-skin syndrome

Question 3

Staph aureus food poisoning

Answer 3

Contamination -> growth -> enterotoxin -> diarrhea
- multiple strains -> different toxins
Toxins - A-E, G, H, I - not F
- heat stable
- A, C = superantigens -> overwhelming IL-1, IL-2, TNF
-> n/v, non-bloody diarrhea (due to cytokines)

Question 4

Toxic shock syndrome

Answer 4

Requires colonization via specific receptor-ligand

• tampon, nasal packing, wound
• > TSST1 (aka enterotoxin F) = superantigen (-> IL1, IL2, TNF)
• > fever, rash, desquamation (hands, feet) -> shock

Question 5

Scalded-skin syndrome

Answer 5

Specific groups of Staph aureus (phage group II)
-> colonization
-> exfoliatins A and B (EtaA, EtaB) - encoded by plasmids
= supertoxin

-> erythema -> epidermis detaches -> exfoliation
Most common in infants

Question 6

Invasive Staph aureus pathogenesis

Answer 6

Adhesion to ECM

• multiple adhesins vs fibrinogen, fibronectin, collagen, PLTs
• matrix exposed at wounds, catheters, disrupted resp, endothelium
• > colonization, immune evasion -> toxins, enzymes -> spread via blood

Toxins, enzymes

• alpha toxin = hemolysin
• leukocidin
• coagulase
• lipase, protease (3 kinds)
• hyaluronidase
• staphylokinase -> fibrinolysis

Immune evasion separate slide

Immune containment -> local abcess
Not contained -> bloodstream -> skin, heart, liver, CNS, etc

Question 7

Staph aureus immune evasion

Answer 7

Key for invasive disease

Protein A = cell wall protein
- binds to IgG Fc (wrong end) -> less complement activation
- B-cell superantigen -> defective IgM production
Enterotoxins - A-E, G, H, I = T-cell superantigens
Capsule polysaccharides = antiphagocytic
Eap/Map - impairs neutrophil recruitment
PV leukocidin (PVL)

Question 8

Staph aureus invasive presentation

Answer 8

Can be local or disseminated
Suppurative, abscess formation

Superficial -> cellulitis
Impetigo (red vesicles)
Folliculitis (hydradenitis suppurtiva = arm pit)
Furuncles, carbuncles, paronychia
Lymphangitis
Wounds, catheters (common!)
Mastitis
Pneumonia (hosp, post-op)
Endocarditis (valve -> L, addict -> R)
Osteomyelitis (traumatic, hematogenous)
Arthritis (children, hematogenous)
Meningitis (traumatic, hematogenous)
Sepsis (where did it originate?)

Question 9

Staph aureus treatment

Answer 9

Abscess = surgical (requires drainage)

Produce penicillinases -> must use synthetic
- dicloxacillin (oral), oxacillin (IV)
Vanco - last resort - may develop intermediate resistance
- now some complete resistance (VanA from enterococcus)
Alternatives - linezolid, daptomycin, ceftaroline, televancin
May develop tolerance (inhibited but not cidal, MBC:MIC)
-> combinations with rifampin, gentamicin

Prevent - isolation, hand-washing
- mupirocin prevents nasal colonization

Question 10

Staph aureus bacteriology

Answer 10

Large yellow colonies
Catalase (+) - vs Strep, Enterococcus
Ferments mannitol
Hemolysin
DNase
Nitrate reductase
Protein A
Teichoic acid
Phage receptor (subtypes)
Non-motile

Question 11

Staph epidermidis bacteriology

Answer 11

Smaller white colonies
No mannitol fermentation
Catalase (-)
Little hemolysis on blood
Sensitive to novobiocin (vs saprophyticus)

Question 12

Staph epidermidis pathogenesis

Answer 12

Normal skin flora - opportunistic

• > colonizes devices efficiently (catheter, implants, etc)
• surface carb -> synthetics -> biofilm
• > slow proliferation -> bloodstream (slower than aureus)

Neonates, dialysis, immunocompromised most susceptible

Question 13

Staph epidermidis clinical

Answer 13

Presentation = indolent, less toxic than S aureus
- low grade fever, pain, discomfort -> bacteremia
- indwelling device
Positive culture + no s/sx = contamination!

Tx:

• remove catheter
• resistant to synthetic penicillins -> vanco
• consider + rifampin or gentamicin if toxic

Question 14

Staph saprophyticus

Answer 14

Coagulase (-), nitrate reductase (-)
Catalase +
Does not ferment mannitol
Resistant to novobiocin (vs epidermidis)

Normal skin flora -> UTI in young (second behind E coli)

• > Bactrim (trimethoprim + sulfamethoxazole)
• > norfloxacin/quinolone